Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome Associated with COVID-19: An Emulated Target Trial Analysis.

Rationale: Whether patients with coronavirus disease (COVID-19) may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. Objectives: To estimate the effect of ECMO on 90-day mortality versus IMV only. Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO versus no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 < 80 or PaCO2 ⩾ 60 mm Hg). We controlled for confounding using a multivariable Cox model on the basis of predefined variables. Measurements and Main Results: A total of 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability on Day 7 from the onset of eligibility criteria (87% vs. 83%; risk difference, 4%; 95% confidence interval, 0-9%), which decreased during follow-up (survival on Day 90: 63% vs. 65%; risk difference, -2%; 95% confidence interval, -10 to 5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand and when initiated within the first 4 days of IMV and in patients who are profoundly hypoxemic. Conclusions: In an emulated trial on the basis of a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and regions with ECMO capacities specifically organized to handle high demand.

Economic impact of avoidable cancer deaths caused by diagnostic delay during the COVID-19 pandemic: A national population-based modelling study in England, UK.

INTRODUCTION: Delays in cancer diagnosis arose from the commencement of non-pharmaceutical interventions (NPI) introduced in the UK in March 2020 in response to the COVID-19 pandemic. Our earlier work predicted this will lead to approximately 3620 avoidable deaths for four major tumour types (breast, bowel, lung, and oesophageal cancer) in the next 5 years. Here, using national population-based modelling, we estimate the health and economic losses resulting from these avoidable cancer deaths. We also compare these with the impact of an equivalent number of COVID-19 deaths to understand the welfare consequences of the different health conditions. METHODS: We estimate health losses using quality-adjusted life years (QALYs) and lost economic productivity using the human capital (HC) approach. The analysis uses linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15-84 years, diagnosed with breast, colorectal, and oesophageal cancer between 1st Jan to 31st Dec 2010, with follow-up data until 31st Dec 2014, and diagnosed with lung cancer between 1st Jan to 31st Dec 31 2012, with follow-up data until 31st Dec 2015. Productivity losses are based on the estimation of excess additional deaths due to cancer at 1, 3 and 5 years for the four cancer types, which were derived from a previous analysis using this dataset. A total of 500 random samples drawn from the total number of COVID-19 deaths reported by the Office for National Statistics, stratified by gender, were used to estimate productivity losses for an equivalent number of deaths (n = 3620) due to SARS-CoV-2 infection. RESULTS: We collected data for 32,583 patients with breast cancer, 24,975 with colorectal cancer, 6744 with oesophageal cancer, and 29,305 with lung cancer. We estimate that across the four site-specific cancers combined in England alone, additional excess cancer deaths would amount to a loss of 32,700 QALYs (95% CI 31,300-34,100) and productivity losses of £103.8million GBP (73.2-132.2) in the next five years. For breast cancer, we estimate a loss of 4100 QALYS (3900-4400) and productivity losses of £23.2 m (18.2-28.6); for colorectal cancer, 15,000 QALYS (14,100-16,000) lost and productivity losses of £35.7 m (22.4-48.7); for lung cancer 10,900 QALYS (9,900-11,700) lost and productivity losses of £38.3 m (14.0-59.9) for lung cancer; and for oesophageal cancer, 2700 QALYS (2300-3,100) lost and productivity losses of £6.6 m (-6 to -17.6). In comparison, the equivalent number of COVID-19 deaths caused approximately 21,450 QALYs lost, as well as productivity losses amounting to £76.4 m (73.5-79.2). CONCLUSION: Premature cancer deaths resulting from diagnostic delays during the first wave of the COVID-19 pandemic in the UK will result in significant economic losses. On a per-capita basis, this impact is, in fact, greater than that of deaths directly attributable to COVID-19. These results emphasise the importance of robust evaluation of the trade-offs of the wider health, welfare and economic effects of NPI to support both resource allocation and the prioritisation of time-critical health services directly impacted in a pandemic, such as cancer care.

The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.

BACKGROUND: Since a national lockdown was introduced across the UK in March, 2020, in response to the COVID-19 pandemic, cancer screening has been suspended, routine diagnostic work deferred, and only urgent symptomatic cases prioritised for diagnostic intervention. In this study, we estimated the impact of delays in diagnosis on cancer survival outcomes in four major tumour types. METHODS: In this national population-based modelling study, we used linked English National Health Service (NHS) cancer registration and hospital administrative datasets for patients aged 15-84 years, diagnosed with breast, colorectal, and oesophageal cancer between Jan 1, 2010, and Dec 31, 2010, with follow-up data until Dec 31, 2014, and diagnosed with lung cancer between Jan 1, 2012, and Dec 31, 2012, with follow-up data until Dec 31, 2015. We use a routes-to-diagnosis framework to estimate the impact of diagnostic delays over a 12-month period from the commencement of physical distancing measures, on March 16, 2020, up to 1, 3, and 5 years after diagnosis. To model the subsequent impact of diagnostic delays on survival, we reallocated patients who were on screening and routine referral pathways to urgent and emergency pathways that are associated with more advanced stage of disease at diagnosis. We considered three reallocation scenarios representing the best to worst case scenarios and reflect actual changes in the diagnostic pathway being seen in the NHS, as of March 16, 2020, and estimated the impact on net survival at 1, 3, and 5 years after diagnosis to calculate the additional deaths that can be attributed to cancer, and the total years of life lost (YLLs) compared with pre-pandemic data. FINDINGS: We collected data for 32 583 patients with breast cancer, 24 975 with colorectal cancer, 6744 with oesophageal cancer, and 29 305 with lung cancer. Across the three different scenarios, compared with pre-pandemic figures, we estimate a 7·9-9·6% increase in the number of deaths due to breast cancer up to year 5 after diagnosis, corresponding to between 281 (95% CI 266-295) and 344 (329-358) additional deaths. For colorectal cancer, we estimate 1445 (1392-1591) to 1563 (1534-1592) additional deaths, a 15·3-16·6% increase; for lung cancer, 1235 (1220-1254) to 1372 (1343-1401) additional deaths, a 4·8-5·3% increase; and for oesophageal cancer, 330 (324-335) to 342 (336-348) additional deaths, 5·8-6·0% increase up to 5 years after diagnosis. For these four tumour types, these data correspond with 3291-3621 additional deaths across the scenarios within 5 years. The total additional YLLs across these cancers is estimated to be 59 204-63 229 years. INTERPRETATION: Substantial increases in the number of avoidable cancer deaths in England are to be expected as a result of diagnostic delays due to the COVID-19 pandemic in the UK. Urgent policy interventions are necessary, particularly the need to manage the backlog within routine diagnostic services to mitigate the expected impact of the COVID-19 pandemic on patients with cancer. FUNDING: UK Research and Innovation Economic and Social Research Council.